Patterns of Relapse in Squamous Cell Carcinoma of the Tonsil - Unilateral vs. Bilateral Radiation in the HPV-Era

Abstract

Objectives: In the pre-human papillomavirus (HPV) era, unilateral radiation therapy (URT) for tonsil cancer was associated with low contralateral failure rates and had less toxicity than bilateral radiation therapy (BRT). This study explores the validity of URT in HPV-positive tonsil cancers.Methods: Tonsil squamous cell carcinomas (SCC) treated (typically with 70 Gy radiation and Cisplatin-based chemotherapy) between 2001 and 2007 were reviewed. Retrospective p16 immunohistochemistry staining was undertaken. Baseline, treatment, and response data were collected.Results: Of 182 patients, 78% were p16-positive, were younger (predominantly male), mostly former or non-smokers, and had a more advanced nodal stage. With a median follow-up of 68 months, contralateral recurrence (CLR) rates were low (3.5% p16-positive versus 2.5% p16-negative, p=0.63). Overall survival (OS) was 74% for p16-positive versus 54% for p16-negative subjects (p=0.01), but all other outcomes were similar. Analysis amongst only p16-positive subjects revealed URT was delivered to 37%, with CLR rates of 7.5% versus 1.1% for those treated with BRT, p=0.05. Of the four p16-positive subjects treated with URT who developed contralateral recurrences, three were managed with neck dissection (two disease-free and one died of lung metastases) and one received palliative radiation to the neck and distant metastatic site. All disease control and survival outcomes were similar between those treated with URT versus BRT.Conclusion: While CLRs remain rare overall, there appears to be a slightly increased rate among HPV-positive subjects treated with URT. However, overall outcomes do not appear to be impacted, suggesting that URT remains a reasonable approach in HPV-positive subjects.

Comparison of unilateral versus bilateral intensity‐modulated radiotherapy for surgically treated squamous cell carcinoma of the palatine tonsil

“…7 Ye et al also reported no recurrences among 11 patients with well-lateralized tonsillar cancer with N2b disease who were treated with unilateral RT. 27 Dan et al reported the results of patients treated with unilateral RT in a community setting including 31 patients with N2b disease, and observed 1 contralateral recurrence in this group. 28 Several other studies also reported no contralateral recurrences.…”

“…In the Rotterdam series, approximately 17% of patients had well‐lateralized tonsillar cancer with N2b disease and 1 contralateral recurrence was reported in a patient with T1N2b disease . Ye et al also reported no recurrences among 11 patients with well‐lateralized tonsillar cancer with N2b disease who were treated with unilateral RT . Dan et al reported the results of patients treated with unilateral RT in a community setting including 31 patients with N2b disease, and observed 1 contralateral recurrence in this group .…”

Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization

“…However, the increase in nodal staging is primarily because of a 5‐fold increase in ipsilateral nodal disease (N2a/b) rather than contralateral N2c disease. Therefore, the indications for unilateral treatment likely remain relevant in the HPV‐positive population . The Washington University reported that 72% of unilateral postoperative patients had HPV‐positive oropharyngeal cancers and none of them failed contralaterally .…”

“…Therefore, the indications for unilateral treatment likely remain relevant in the HPV-positive population. 28,29 The Washington University reported that 72% of unilateral postoperative patients had HPV-positive oropharyngeal cancers and none of them failed contralaterally. 23 In our subset of p16-positive tonsillar cancers, none failed contralaterally.…”

Ipsilateral neck radiotherapy in N2b well‐lateralized tonsil cancer – Approach with caution

“…Previous series reporting outcomes of patients with tonsillar SCC treated with ipsilateral RT have reported low rates of CNR . A combined analysis of these ipsilateral neck RT studies showed a CNR rate of 1.9% for the N0‐N2a subpopulation and 4.8% for those with N2b disease .…”